1. Field of the Invention
The present invention relates to a microchip reactor for use in an analytical instrument and, more particularly, to a microchip reactor capable of performing reaction kinetics analysis.
2. Description of Related Art
Technology for mixing and reacting plural substances in a very narrow space is known as microchip technology or microreactor technology. It is expected that this technology will be put into practical use in order to increase the speed of chemical reactions or to enhance the efficiencies of the reactions.
Microchip reactors having microchannels therein used for chemical reactions are often made of glass to have sufficient chemical resistance. However, it is difficult to connect a tube for directly introducing a synthesis reagent into a microchannel of a microchip made of glass. Thus, it is customary that the microchip is held by a holder and then the tube is connected with the holder by a connector.
O-rings are often used to prevent liquid leakage. Substances dissolving out of rubber products and dead volumes often present problems. In one method, an O-ring is bonded to the glass surface with adhesive. However, depending on the used solvent, the adhesive may dissolve out and other problems may take place. Furthermore, a threaded structure used in connecting a tube employed in a liquid chromatograph can be made of glass. Unfortunately, sophisticated skill is necessary to machine the threaded structure of glass, increasing the cost.
In addition, depending on the kind of synthesis reaction, a reagent solution having a high viscosity may be used. After the solution is introduced, the flow passage may be clogged up by the solution. Especially, the passage portions close to the connector tend to be clogged up.
With respect to microchip reactors used for chemical synthesis, some commercial products have been already sold by some manufacturers. The products are chiefly made of glass. A commercially available microchip for the mixing of two reagents is shown in FIGS. 1A, 1B and 1C. The microchip made of glass is composed of two plates. A microchannel is formed in one of the plates (see FIG. 1A). A liquid inlet port and a liquid exit port are formed in the other. The two plates are bonded together by thermocompression.
The microchip is held to a holder (see FIG. 1B). Tubes for introduction of reagents are connected using connectors (see FIG. 1C). The tubes are connected with syringe pumps. Reagent solutions are introduced into the microchip by the syringe pumps. The introduced solutions are made to meet in the Y-shaped portion of the flow channel and are mixed together. The solutions are reacted in the downstream tube portion. Thus, reaction products are synthesized.
A well-known method of detecting reaction products on-line is to use a thermal lens microscope. Where a measurement is made using a mass spectrometer (MS) or a nuclear magnetic resonance spectrometer (NMR) to perform structural analysis of reaction products, the reaction products must be captured at the exit of the microchip. Then, the sample must be introduced into the MS or NMR off-line.
Today, research is being carried out vigorously in an attempt to realize an on-line connection between a microchip or microreactor to which various functions are added and an MS or NMR having excellent qualitative analysis capabilities. The one-line connection is used for analysis. There are the following examples of reports about research.
(1) Microchip-NMR
As shown in FIG. 2, a circular liquid reservoir is formed on a flow channel in a microchip. A microcoil is placed close to the reservoir. A trace amount of sample is measured. This research is found in a report at monographic level. Microcoils and microprobes dedicated for microchips are at the research level. There is almost no application to synthesis.
(2) Flow NMR
Reaction reagents are mixed and reacted using a static mixer or the like. The reaction liquid is introduced to a flow NMR probe via a line, and NMR measurements are performed. This research is at a practical level. The flow NMR probe is necessary for the measurements. The long distance from the reaction portion to the portion inside the NMR magnet irradiated with an RF magnetic field is a disadvantage.
(3) Microchip-MS
As shown in FIG. 3, when a microchip is fabricated, a nanoelectrospray nozzle is integrated with the microchip. Mass analysis is enabled by applying a high voltage to the nozzle. This technique finds wider applications in biochemical applications than in synthesis chemistry.